tbuckley/cabot-search huggingface dataset:
Safety Monitoring of JYNNEOS Vaccine During the 2022 Mpox Outbreak — United States, May 22–October 21, 2022
Authors: Jonathan Duffy, Paige Marquez, Pedro Moro, Eric Weintraub, Yon Yu, Peter Boersma, James G. Donahue, Jason M. Glanz, Kristin Goddard, Simon J. Hambidge, Bruno Lewin, Ned Lewis, Douglas Rouse, Tom Shimabukuro
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended in the United States for persons exposed to or at high risk for exposure to Monkeypox virus during the 2022 monkeypox (mpox) outbreak (1).JYNNEOS is a live, nonreplicating viral vaccine licensed for the prevention of smallpox and mpox in adults aged ≥18 years, administered as a 0.5-mL 2-dose series given 28 days apart by subcutaneous injection (2).On August 9, 2022, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for administration of 0.1 mL doses by intradermal injection for adults aged ≥18 years as a strategy to increase vaccine supply, and administration of 0.5 mL doses subcutaneously for persons aged <18 years (3).During May 22-October 21, 2022, a total of 987,294 JYNNEOS vaccine doses were administered in the United States.CDC has monitored JYNNEOS vaccine safety using the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for vaccine recipients of all ages, and through single-patient emergency Investigational New Drug (EIND) procedures for persons aged <18 years vaccinated before August 9, 2022.The most common adverse health events reported to VAERS for adults were nonserious and included injection site reactions, which was consistent with the prelicensure studies.Adverse health events were reported at similar rates for doses received by intradermal and subcutaneous administration.Serious adverse events were rare in adults, and no serious adverse events have been identified among persons aged <18 years.Overall, postlicensure and postauthorization surveillance to date support JYNNEOS vaccine safety.VAERS is a national passive surveillance system for adverse events after vaccination (4).VAERS accepts reports from health care providers, vaccine manufacturers, and the public.The JYNNEOS EUA requires reporting the following events to VAERS: vaccine administration errors (whether or not associated with an adverse event), serious adverse events (irrespective of attribution to vaccination), and cases of cardiac, thromboembolic, and neurovascular events.*Reported signs and * The JYNNEOS EUA requires health care providers and the vaccine manufacturer to report serious adverse events (irrespective of attribution to vaccination), and cases of cardiac, thromboembolic, and neurovascular events.Health care providers are also required to report vaccine administration errors (whether or not associated with an adverse event).Based on the Code of Federal Regulations, a serious adverse event is defined as occurring if one of the following is reported: death, life-threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly, or birth defect.
Ann Robinson’s research reviews—8 December 2022
Authors: Ann Robinson
Journal: BMJ (2022)

A bout de souffleMy mum was a smoker, and watching her struggle to breathe as chronic obstructive pulmonary disease (COPD) took hold was heartbreaking.When your main activity of daily living is breathing, it doesn't leave much physical or psychological strength for anything else.The treatment options are limited and increasingly ineffective as the condition progresses.Low dose opioids are commonly tried for symptom control, but evidence is sparse.A small but notable Australian trial of 156 people with COPD and chronic breathlessness (MRC modified breathlessness scale score 3 or 4) found that a week of daily, low dose, oral, extended release morphine (8 or 16 mg/day) didn't significantly improve the intensity of worst breathlessness compared with placebo.The daily step count didn't improve either, even at higher doses of up to 48 mg/day.More people who received morphine had serious adverse events such as increased breathlessness, morphine related symptoms, and respiratory failure than those taking placebo (33% v 12%), and overall rates of adverse events that emerged during treatment with 8 or 16 mg/day of morphine or with placebo were high (64%, 78%, and 48%).The high rates of side effects may partly explain why only 42% completed three weeks of treatment and the high dropout rate across all groups.
PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A–producing γδ T cells
Authors: Sarah C. Edwards, Ann Hedley, Wilma H.M. Hoevenaar, Robert Wiesheu, Teresa Glauner, Anna Kilbey, Robin Shaw, Katerina Boufea, Nizar Batada, Shinya Hatano, Yasunobu Yoshikai, Karen Blyth, Crispin Miller, Kristina Kirschner, Seth B. Coffelt
Journal: The Journal of Experimental Medicine (2022)

IL-17A-producing γδ T cells in mice consist primarily of Vγ6+ tissue-resident cells and Vγ4+ circulating cells. How these γδ T cell subsets are regulated during homeostasis and cancer remains poorly understood. Using single-cell RNA sequencing and flow cytommetry, we show that lung Vγ4+ and Vγ6+ cells from tumor-free and tumor-bearing mice express contrasting cell surface molecules as well as distinct co-inhibitory molecules, which function to suppress their expansion. Vγ6+ cells express constitutively high levels of PD-1, whereas Vγ4+ cells upregulate TIM-3 in response to tumor-derived IL-1β and IL-23. Inhibition of either PD-1 or TIM-3 in mammary tumor-bearing mice increased Vγ6+ and Vγ4+ cell numbers, respectively. We found that genetic deletion of γδ T cells elicits responsiveness to anti-PD-1 and anti-TIM-3 immunotherapy in a mammary tumor model that is refractory to T cell checkpoint inhibitors, indicating that IL-17A-producing γδ T cells instigate resistance to immunotherapy. Together, these data demonstrate how lung IL-17A-producing γδ T cell subsets are differentially controlled by PD-1 and TIM-3 in steady-state and cancer.
Insights into the clinical outcomes of bronchiectasis
Authors: Zhen-feng He, Shan-shan Zha, Cui-xia Pan, Nan-shan Zhong, Wei-jie Guan
Journal: European Respiratory Journal (2022)

<b>There are queries regarding data from EMBARC-India due to an imbalance of patient baseline characteristics, confounded by different clinical statuses, other co-existing chronic respiratory diseases and the rate of inhaled corticosteroid use</b>http://bit.ly/3X3CxzN
Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond
Authors: Marcus A. Mall, Gerard J. Criner, Marc Miravitlles, Steven M. Rowe, Claus F. Vogelmeier, David J. Rowlands, Matthias Schoenberger, Pablo Altman
Journal: European Respiratory Journal (2022)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel for transport of chloride and bicarbonate anions. Functional roles of CFTR have been identified in a broad range of cell types including epithelial, endothelial, immune and structural cells. While CFTR has been investigated largely in the context of inborn dysfunction in cystic fibrosis, recent evidence shows that CFTR is also affected by acquired dysfunction in COPD. In patients with COPD and smokers, CFTR impairment has been demonstrated in the upper and lower airways, sweat glands and intestines, suggesting both pulmonary and systemic defects. Cigarette smoke, a key factor in COPD development, is the major cause of acquired CFTR dysfunction. Inflammation, bacterial byproducts and reactive oxygen species can further impair CFTR expression and function. CFTR dysfunction could contribute directly to disease manifestation and progression of COPD including disturbed airway surface liquid homeostasis, airway mucus obstruction, pathogen colonisation and inflammation. Mucus plugging and neutrophilic inflammation contribute to tissue destruction, development of dysfunction at the level of the small airways and COPD progression. Acquired CFTR dysfunction in extrapulmonary organs could add to common comorbidities and the disease burden. This review explores how CFTR dysfunction may be acquired and its potential effects on patients with COPD, particularly those with chronic bronchitis. The development of CFTR potentiators and the probable benefits of CFTR potentiation to improve tissue homeostasis, reduce inflammation, improve host defence and potentially reduce remodelling in the lungs will be discussed.
Publisher Correction: Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors
Authors: Huipeng Li, Elise T. Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J. K. Wee, Axel M. Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar
Journal: Nature Genetics (2022)
More than<i>Mycobacterium tuberculosis:</i>site-of-disease microbial communities, and their functional and clinical profiles in tuberculous lymphadenitis
Authors: Georgina R Nyawo, Charissa C Naidoo, Benjamin Wu, Imran Sulaiman, Jose C Clemente, Yonghua Li, Stephanie Minnies, Byron W P Reeve, Suventha Moodley, Cornelia Rautenbach, Colleen Wright, Shivani Singh, Andrew Whitelaw, Pawel Schubert, Robin Warren, Leopoldo Segal, Grant Theron
Journal: Thorax (2022)

Background Lymphadenitis is the most common extrapulmonary tuberculosis (EPTB) manifestation. The microbiome is important to human health but uninvestigated in EPTB. We profiled the site-of-disease lymph node microbiome in tuberculosis lymphadenitis (TBL). Methods Fine-needle aspiration biopsies were collected from 158 pretreatment presumptive TBL patients in Cape Town, South Africa. 16S Illumina MiSeq rRNA gene sequencing was done. Results We analysed 89 definite TBLs (dTBLs) and 61 non-TBLs (nTBLs), which had similar α- but different β-diversities (p= 0.001 ). Clustering identified five lymphotypes prior to TB status stratification: Mycobacterium- dominant , Prevotella- dominant and Streptococcus- dominant lymphotypes were more frequent in dTBLs whereas a Corynebacterium -dominant lymphotype and a fifth lymphotype (no dominant taxon) were more frequent in nTBLs. When restricted to dTBLs, clustering identified a Mycobacterium -dominant lymphotype with low α-diversity and non- Mycobacterium -dominated lymphotypes (termed Prevotella-Corynebacterium , Prevotella-Streptococcus ). The Mycobacterium dTBL lymphotype was associated with HIV-positivity and features characteristic of severe lymphadenitis (eg, larger nodes). dTBL microbial communities were enriched with potentially proinflammatory microbial short-chain fatty acid metabolic pathways (propanoate, butanoate) vs nTBLs. 11% (7/61) of nTBLs had Mycobacterium reads BLAST-confirmed as Mycobacterium tuberculosis complex. Conclusions TBL at the site-of-disease is not microbially homogeneous. Distinct microbial community clusters exist that, in our setting, are associated with different clinical characteristics, and immunomodulatory potentials. Non- Mycobacterium -dominated dTBL lymphotypes, which contain taxa potentially targeted by TB treatment, were associated with milder, potentially earlier stage disease. These investigations lay foundations for studying the microbiome’s role in lymphatic TB. The long-term clinical significance of these lymphotypes requires prospective validation.
How to make Eczema Care Online freely available
Authors: Miriam Santer, Lucy Yardley, Ingrid Muller, Amanda Roberts, Kim S Thomas
Journal: BMJ (2022)

Eczema management can be challenging for patients, since it involves avoiding triggers, using emollient regularly, and intermittent use of topical anti-inflammatory agents such as corticosteroids.It can be difficult for healthcare professionals to explain and resolve eczema concerns within time-limited consultations.We developed Eczema Care Online (EczemaCareOnline.org.uk), an online behavioural intervention to provide self-management support for people with eczema in response to the need for self-management support interventions that are rigorously developed, informed by theory and evidence, and co-produced with diverse users to maximise accessibility and usability.Our recent research study evaluated the effectiveness of interventions for parents, carers, and young people. 1 We found that they provided a small but significant benefit in eczema severity at 24 weeks, which was sustained at 52 weeks for both parents and carers of children and for young people, at minimal cost, and with no identifiable harms.As eczema affects up to 20% of children and up to 10% of adults, use of such interventions could translate to substantial population benefit.
Multi-region sequencing with spatial information enables accurate heterogeneity estimation and risk stratification in liver cancer
Authors: Chen Yang, Senquan Zhang, Zhuoan Cheng, Zhicheng Liu, Linmeng Zhang, Kai Jiang, Haigang Geng, Ruolan Qian, Jun Wang, Xiaowen Huang, Mo Chen, Zhe Li, Wenxin Qin, Qiang Xia, Xiaonan Kang, Cun Wang, Hualian Hang
Journal: Genome Medicine (2022)

Abstract Background Numerous studies have used multi-region sampling approaches to characterize intra-tumor heterogeneity (ITH) in hepatocellular carcinoma (HCC). However, conventional multi-region sampling strategies do not preserve the spatial details of samples, and thus, the potential influences of spatial distribution on patient-wise ITH (represents the overall heterogeneity level of the tumor in a given patient) have long been overlooked. Furthermore, gene-wise transcriptional ITH (represents the expression pattern of genes across different intra-tumor regions) in HCC is also under-explored, highlighting the need for a comprehensive investigation. Methods To address the problem of spatial information loss, we propose a simple and easy-to-implement strategy called spatial localization sampling (SLS). We performed multi-region sampling and sequencing on 14 patients with HCC, collecting a total of 75 tumor samples with spatial information and molecular data. Normalized diversity score and integrated heterogeneity score (IHS) were then developed to measure patient-wise and gene-wise ITH, respectively. Results A significant correlation between spatial and molecular heterogeneity was uncovered, implying that spatial distribution of sampling sites did influence ITH estimation in HCC. We demonstrated that the normalized diversity score had the ability to overcome sampling location bias and provide a more accurate estimation of patient-wise ITH. According to this metric, HCC tumors could be divided into two classes (low-ITH and high-ITH tumors) with significant differences in multiple biological properties. Through IHS analysis, we revealed a highly heterogenous immune microenvironment in HCC and identified some low-ITH checkpoint genes with immunotherapeutic potential. We also constructed a low-heterogeneity risk stratification (LHRS) signature based on the IHS results which could accurately predict the survival outcome of patients with HCC on a single tumor biopsy sample. Conclusions This study provides new insights into the complex phenotypes of HCC and may serve as a guide for future studies in this field.
Is There a Role for Thromboprophylaxis in Selected Outpatients With COVID-19?
Authors: Anastasios Kollias, Konstantinos G. Kyriakoulis, Evangelos Dimakakos
Journal: JAMA Internal Medicine (2022)

JunQing Xie, BSMed, MSc; Albert Prats-Uribe, DPhil; Qi Feng, PhD; YunHe Wang, MSc; Dipender Gill, MD, PhD; Roger Paredes, MD, PhD; Dani Prieto-Alhambra, MD, PhD
Association of Linezolid With Risk of Serotonin Syndrome in Patients Receiving Antidepressants
Authors: Anthony D. Bai, Susan McKenna, Heather Wise, Mark Loeb, Sudeep S. Gill
Journal: JAMA Network Open (2022)

Importance Linezolid has the potential to interact with some antidepressants, leading to serotonin syndrome. However, few empirical data support warnings for patients taking antidepressants to avoid linezolid. Objectives To examine the incidence of serotonin syndrome in patients receiving oral linezolid and how concomitant antidepressant treatment changes this risk. Design, Setting, and Participants This population-based, retrospective cohort study used linked administrative databases at ICES to collect data from outpatients 66 years or older in Ontario, Canada, who were prescribed oral linezolid for any duration from October 1, 2014, to January 1, 2021, with follow-up to 30 days (January 31, 2021). Exposures The use of antidepressants while receiving linezolid therapy vs no antidepressant use while receiving linezolid therapy. Main Outcomes and Measures The primary outcome was clinically significant serotonin syndrome based on a physician diagnosis, Sternbach criteria, or the Hunter Serotonin Toxicity Criteria within 30 days of starting oral linezolid treatment. Secondary outcomes were altered mental status, hospitalization, or death within 30 days of starting linezolid treatment. Results The study included 1134 patients (age ranges, 66-69 years for 225 patients [19.8%], 70-79 years for 473 patients [41.7%], and ≥80 years for 436 patients [38.4%]; 595 [52.5%] male) who were prescribed linezolid. Of 1134 patients, 215 (19.0%) were also taking antidepressants. Serotonin syndrome occurred in fewer than 6 patients (&amp;amp;lt;0.5%). The number of serotonin syndrome cases were fewer in the antidepressant group. In a propensity score–matched cohort, the adjusted risk difference for serotonin syndrome between the antidepressant group and the no antidepressant group was −1.2% (95% CI, −2.9% to 0.5%). There were similar rates of altered mental status, hospitalization, and death between the propensity score–matched groups. Conclusions and Relevance In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely. Concurrent antidepressants did not significantly increase the risk of serotonin syndrome. These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction.
Association Between Patient Satisfaction With Their Patient-Physician Relationship and Completion of Bariatric Surgery by Race and Ethnicity Among US Adults
Authors: Luyu Xie, Jaime P. Almandoz, M. Sunil Mathew, Jeffrey N. Schellinger, Olivia Kapera, Sophia Ngenge, Elisa Morales Marroquin, Carrie McAdams, Sachin Kukreja, Benjamin Schneider, Sarah E. Messiah
Journal: JAMA Network Open (2022)

Importance Metabolic and bariatric surgery (MBS) is an effective and safe treatment for obesity and its comorbidities, but less than 50% of those who are eligible and referred for MBS complete the procedure. The patient-physician relationship could be a decisive factor in the decision to complete MBS; however, this relationship has not been explored, particularly among racially and ethnically diverse populations. Objective To examine the association between patient-reported satisfaction with their patient-physician relationship and MBS completion by self-reported racial and ethnic group. Design, Setting, and Participants This prospective cohort study included 408 patients who were referred to a bariatric surgeon or obesity medicine program between July 24, 2019, and May 19, 2022. Exposure Patient satisfaction with their physician was measured by 7 dimensions (general satisfaction, technical quality, interpersonal manner, communication, financial aspects, time spent with physician, and accessibility and convenience) using the Patient Satisfaction Questionnaire Short Form. Main Outcomes and Measures Completion status for MBS (yes or no). Results A total of 408 patients (mean [SD] age, 47.3 [11.6] years; among 366 with data available, 317 [86.6%] women and 49 [13.4%] men) were included in the study. Of 363 patients with data available on race and ethnicity, 66 were Hispanic/Latinx (18.2%), 136 (37.5%) were non-Hispanic Black, 146 (40.2%) were non-Hispanic White, and 15 (4.1%) were other race or ethnicity. A total of 124 patients (30.4%) completed MBS. Overall, the mean (SD) patient satisfaction score was significantly greater in MBS completers vs noncompleters (3.86 [0.56] vs 3.61 [0.64]; P &amp;amp;lt; .001). Multivariable logistic regression analysis showed technical quality was the most significant factor for MBS completion (adjusted odds ratio [aOR], 1.99 [95% CI, 1.24-3.19]), followed by communication (aOR, 1.78 [95% CI, 1.16-2.72]) and accessibility and convenience (aOR, 1.61 [95% CI, 1.03-2.53]). The interaction between racial and ethnic groups and patient satisfaction was not significant (eg, mean [SD] score for Hispanic/Latinx completers, 3.95 [0.55] vs 3.77 [0.60] for non-Hispanic White completers; P = .46 for interaction). Conclusions and Relevance These findings suggest that there is an association between patient satisfaction with the patient-physician relationship and the decision to complete MBS regardless of race and ethnicity. These findings have important implications for strategies to improve the proportion of qualified patients who complete MBS to achieve improved health outcomes.
A 62-Year-Old Woman With a Large Abdominal Mass
Authors: Luigi Marano, Ludovico Carbone, Franco Roviello
Journal: JAMA (2022)

A 62-year-old nulligravida woman had 10 months of progressive abdominal distension, diffuse abdominal pain, and 25-kg weight gain. She had no nausea or vomiting, hematochezia, or stool changes; pelvic and abdominal examination showed a large abdominal mass extending from the epigastrium to the pelvis but no other abnormalities; results of laboratory testing, including cancer antigen levels, were unremarkable. What is the diagnosis and what would you do next?
Effect of Saline vs Gluconate/Acetate–Buffered Solution vs Lactate-Buffered Solution on Serum Chloride Among Children in the Pediatric Intensive Care Unit
Authors: Sainath Raman, Kristen S. Gibbons, Adrian Mattke, Andreas Schibler, Peter Trnka, Melanie Kennedy, Renate Le Marsney, Luregn J. Schlapbach
Journal: JAMA Pediatrics (2022)

Most children admitted to pediatric intensive care units (PICUs) receive intravenous fluids. A recent systematic review suggested mortality benefit in critically ill adults treated with balanced solutions compared with sodium chloride, 0.9% (saline). There is a lack of clinically directive data on optimal fluid choice in critically ill children.
Trends in Homicide Rates for US Children Aged 0 to 17 Years, 1999 to 2020
Authors: Rebecca F. Wilson, Beverly L. Fortson, Hong Zhou, Bridget H. Lyons, Kameron J. Sheats, Carter J. Betz, Janet M. Blair, Shannon Self-Brown
Journal: JAMA Pediatrics (2022)

Homicide is a leading cause of death among children in the US.
Stemming Medicare Spending on Discarded Drugs—Waste Not, Want Not?
Authors: Cary P. Gross, Stacie B. Dusetzina
Journal: JAMA Internal Medicine (2022)

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